Single-round selection yields a unique retroviral envelope utilizing GPR172A as its host receptor

• DOI: 10.1073/pnas.0809741106
• Publication Date: 2009-03-24T01:30:41Z
• Authors: Peter M. Mazari; Daniela Linder-Basso; Anindita Sarangi; Yehchung Chang; Monica J. Roth
• Keywords: 0301 basic medicine; Osteosarcoma; 03 medical and health sciences; Binding Sites; Viral Envelope Proteins; Leukemia Virus, Feline; Receptors, Virus; Amino Acid Sequence; Peptide Fragments; Receptors, G-Protein-Coupled; 3. Good health

The recognition by a viral envelope of its cognate host-cell receptor is the initial critical step in defining the viral host-range and tissue specificity. This study combines a single-round of selection of a random envelope library with a parallel cDNA screen for receptor function to identify a distinct retroviral envelope/receptor pair. The 11-aa targeting domain of the modified feline leukemia virus envelope consists of a constrained peptide. Critical to the binding of the constrained peptide envelope to its cellular receptor are a pair of internal cysteines and an essential Trp required for maintenance of titers >10 5 lacZ staining units per milliliter. The receptor used for viral entry is the human GPR172A protein, a G-protein-coupled receptor isolated from osteosarcoma cells. The ability to generate unique envelopes capable of using tissue- or disease-specific receptors marks an advance in the development of efficient gene-therapy vectors.